Ampicillin/ceftriaxone vs. β-lactam/aminoglycoside combination therapy for Enterococcus faecalis infective...

Enterococcus faecalis infective endocarditis (EFIE) remains a formidable infection requiring prolonged antimicrobial therapy. Although β-lactam/aminoglycoside (BL + AG) combination therapy has long been regarded as the standard treatment, AG-associated toxicities pose a major clinical dilemma. Recently, dual β-lactam therapy with ampicillin/ceftriaxone (A + C) has become an established treatment option. This systematic review and meta-analysis aimed to compare the efficacy and safety of A + C versus BL + AG therapy in patients with EFIE.

A literature search was conducted using PubMed, the Cochrane Library, Web of Science, and ClinicalTrials.gov. Clinical studies comparing A + C versus BL + AG for EFIE were included. Primary outcomes were mortality and relapse rates. Secondary outcomes included overall adverse events, renal adverse events, ototoxicity/vestibular toxicity, skin rash, Clostridioides difficile diarrhea, and regimen changes or discontinuation. Pooled ORs and 95% CIs were estimated utilizing random-effects models.

Six studies involving 619 patients with EFIE were included. Cumulative mortality (OR 1.10, 95% CI: 0.73-1.65) and relapse rates (OR 1.08, 95% CI: 0.39-3.01) did not differ significantly between A + C and BL + AG. However, A + C was associated with significantly lower incidences of total adverse events (OR 0.20, 95% CI: 0.08-0.53), renal adverse events (OR 0.34, 95% CI: 0.19-0.58), ototoxicity/vestibular toxicity (OR 0.07, 95% CI: 0.01-0.37), and antibiotic regimen change (OR 0.20, 95% CI: 0.10-0.39) or discontinuation (OR 0.17, 95% CI: 0.05-0.56).

A + C therapy was associated with a more favorable safety profile than BL + AG therapy, with no significant differences in efficacy, mortality, or relapse in patients with EFIE. These findings support the use of A + C as an important therapeutic option for patients at increased risk of AG-associated toxicity.